Schizophrenic disorder is an extremely severe mental illness, lack of contact with reality, hallucinations, delusions and abnormal thinking, social functions significantly damaged. Schizophrenic disorder is a worldwide public hygiene issue; its total morbidity rate throughout the world (including China) is about 0.8-1%. The peak age of onset of schizophrenic disorder is 18˜25 years old for men and 26˜45 years old for women. However, patients having an onset during childhood, adolescence or even old age are also not rare. For different patients the severity and clinical manifestation of their symptoms differ from one another. Overall, the following three groups of symptoms can be summarized: positive symptoms, including hallucinations and delusions, agitation, paranoia, thinking disturbance and dystropy; negative symptoms, including affective blunting, uncommunicativeness, lack of interest, anhedonia andeccentric loner; cognitive deficits, including incapability to focus attention, severe decline of memory and incapability to behave as planned. One group or all the symptoms above may be present in a patient; these symptoms are usually relatively severe, which significantly affect work, interpersonal communication, and even personal life management of a patient. The general purpose of schizophrenic disorder treatment is to alleviate symptoms, prevent recurrence, restore functional defects, as much as possible to promote recovery and enhance life quality.
Currently drugs for treating schizophrenic disorder clinically may be mainly divided into two types: the first generation of anti-schizophrenic drugs (traditional antipsychotics). Such drugs mainly include selective dopamine D2 receptor antagonists, wherein the typical drugs are Haloperidol and Chlorpromazine and the like. These drugs have a certain therapeutic effect on the positive symptoms of schizophrenic disorder, but do not have any effect on the negative symptoms and cognitive deficits. Further, these drugs may lead to severe adverse reactions, such as extrapyramidal side effect, muscular rigidity and weight gain, etc. The second generation of anti-schizophrenic drugs (atypical antipsychotics). These drugs primarily are 5-hydroxytryptamine 5-HT2 receptor antagonists and dopamine D2 receptor antagonists, wherein the typical drugs for example are Olanzepine, Risperidone, Aripiprazole, Quetiapine and Clozapine. The second generation of atypical anti-schizophrenic drugs has a similar therapeutic effect on the positive symptoms of schizophrenic disorder to the first generation of anti-schizophrenic drugs, but has significantly less side effects such as extrapyramidal side effects.
At present anti-schizophrenic drugs used in clinic, particularly the second generation of atypical anti-schizophrenic drugs has a certain therapeutic effect on the positive symptoms of schizophrenic disorder, can alleviate or eliminate symptoms like hallucinations, delusions and thinking disturbance, etc. After the acute symptoms are eliminated, maintenance of antipsychotics can reduce the possibility of recurrence. However, almost all the clinical drugs have no significant therapeutic effect on the negative symptoms and cognitive deficits of schizophrenic disorder. Aripiprazole which is newly listed, as shown by the clinical study results, the drug may have a certain degree of therapeutic effect on the negative symptoms of schizophrenic disorder, but the therapeutic effect thereof is still non-significant and remains to be further investigated by clinical study. Additionally, anti-schizophrenic drugs can cause obvious adverse reactions, e.g. can lead to sedation, muscular rigidity, tremor and weight gain. Meanwhile these antipsychotics may cause tardive dyskinesia, a behavior which is characterized involuntarily by lip and tongue shrinkage, or twisting dyskinesia in arms and legs. Even after drug withdraw, the tardive dyskinesia would not disappear and lack of effective treatment measures.
Short-term prognosis (within one year) of schizophrenic disorder depends on the patient adherence to treatment. If without drug maintenance treatment, 70%˜80% of schizophrenic disorder will relapse within 12 months and may attack again. Drug maintenance may reduce the recurrence rate of the present disease down to about 30%.
Long-term prognosis of schizophrenic disorder greatly varies, wherein ⅓ of patients may obtain significant and sustained improvement, and for another ⅓ of patients, conditions are partially improved with intermittent onsets and left with disabilities, and for the remaining ⅓ of patients, conditions are severe with obvious disabilities. Factors of good prognosis include patients with acute onset, late age of onset, good social skills before onset, and paranoid or positive schizophrenic disorder. Factors of poor prognostic include patients with early age of onset, poor social or professional skills before onset, positive family history of schizophrenic disorder as well as hebephrenic or negative schizophrenic disorder.
CN101616592A has disclosed a benzotriazinone compound for enhancing glutamatergic synaptic responses, which may be used to prevent and treat cerebral insufficiency, for example various diseases such as dementia, schizophrenic disorder and the like. CN101035760A has disclosed a compound for enhancing glutamate receptors, which can be used to treat schizophrenic disorder. CN1535980A has disclosed a novel compound having inhibitory activity against glycine transporter, useful to treat schizophrenic disorder.
Currently, new methods for treating schizophrenic disorder are still expected in the art.